The Effectiveness of Natural Diarylheptanoids against Trypanosoma cruzi: Cytotoxicity, Ultrastructural Alterations and Molecular Modeling Studies
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2016 |
| Outros Autores: | , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/17889 |
Resumo: | Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ); Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES); Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq); The State of São Paulo Research Foundation (FAPESP). |
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Santiago, Vitor SuethMoraes, Julliane de B BSobral Alves, Eliomara SousaSantos, Marcos André Vannier dosLima, Célio Geraldo Freire deCastro, Rosane NoraSilva, Gustavo Peron MendesDel Cistia, Catarina de NigrisMagalhães, Luma GodoyAndricopulo, Adriano DefiniSant'Anna, Carlos Mauricio Rabello deRicardo, Debora DecotéLima, Marco Edilson Freire de2017-02-23T13:49:11Z2017-02-23T13:49:11Z2016SANTIAGO, V. S. et al. The Effectiveness of Natural Diarylheptanoids against Trypanosoma cruzi: Cytotoxicity, Ultrastructural Alterations and Molecular Modeling Studies. Plos One, v. 11, n. 9, e0162926, 2016.1932-6203https://www.arca.fiocruz.br/handle/icict/1788910.1371/journal.pone.0162926Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ); Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES); Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq); The State of São Paulo Research Foundation (FAPESP).Universidade Federal Rural do Rio de Janeiro. Instituto de Ciências Exatas. Departamento de Química. Seropédica, RJ, BrasilUniversidade Federal Rural do Rio de Janeiro. Instituto de Veterinária. Departamento de Microbiologia e Imunologia Veterinária. Seropédica, RJ, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Biologia Parasitária. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Biologia Parasitária. Salvador, BA, BrasilUniversidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Ilha do Fundão. Rio de Janeiro, RJ, BrasilUniversidade Federal Rural do Rio de Janeiro. Instituto de Ciências Exatas. Departamento de Química. Seropédica, RJ, BrasilUniversidade Federal Rural do Rio de Janeiro. Instituto de Ciências Exatas. Departamento de Química. Seropédica, RJ, BrasilUniversidade Federal Rural do Rio de Janeiro. Instituto de Ciências Exatas. Departamento de Matemática. Seropédica, RJ, BrasilUniversidade de São Paulo. Instituto de Física. Centro de Pesquisa e Inovação em Biodiversidade e Fármacos. Laboratório de Química Medicinal e Computacional. São Carlos, São Carlos, SP, BrasilUniversidade de São Paulo. Instituto de Física. Centro de Pesquisa e Inovação em Biodiversidade e Fármacos. Laboratório de Química Medicinal e Computacional. São Carlos, São Carlos, SP, BrasilUniversidade Federal Rural do Rio de Janeiro. Instituto de Ciências Exatas. Departamento de Química. Seropédica, RJ, BrasilUniversidade Federal Rural do Rio de Janeiro. Instituto de Veterinária. Departamento de Microbiologia e Imunologia Veterinária. Seropédica, RJ, BrasilUniversidade Federal Rural do Rio de Janeiro. Instituto de Ciências Exatas. Departamento de Química. Seropédica, RJ, BrasilCurcumin (CUR) is the major constituent of the rhizomes of Curcuma longa and has been widely investigated for its chemotherapeutic properties. The well-known activity of CUR against Leishmania sp., Trypanosoma brucei and Plasmodium falciparum led us to investigate its activity against Trypanosoma cruzi. In this work, we tested the cytotoxic effects of CUR and other natural curcuminoids on different forms of T. cruzi, as well as the ultrastructural changes induced in epimastigote form of the parasite. CUR was verified as the curcuminoid with more significant trypanocidal properties (IC50 10.13 μM on epimastigotes). Demethoxycurcumin (DMC) was equipotent to CUR (IC50 11.07 μM), but bisdemethoxycurcumin (BDMC) was less active (IC50 45.33 μM) and cyclocurcumin (CC) was inactive. In the experiment with infected murine peritoneal macrophages all diarylheptanoids were more active than the control in the inhibition of the trypomastigotes release. The electron microscopy images showed ultrastructural changes associated with the cytoskeleton of the parasite, indicating tubulin as possible target of CUR in T. cruzi. The results obtained by flow cytometry analysis of DNA content of the parasites treated with natural curcuminoids suggested a mechanism of action on microtubules related to the paclitaxel`s mode of action. To better understand the mechanism of action highlighted by electron microscopy and flow cytometry experiments we performed the molecular docking of natural curcuminoids on tubulin of T. cruzi in a homology model and the results obtained showed that the observed interactions are in accordance with the IC50 values found, since there CUR and DMC perform similar interactions at the binding site on tubulin while BDMC do not realize a hydrogen bond with Lys163 residue due to the absence of methoxyl groups. These results indicate that trypanocidal properties of CUR may be related to the cytoskeletal alterations.engPublic Library of ScienceTrypanosoma cruziRecursos naturaisCurcuminaCitometria de fluxoModelagemTrypanosoma cruziNatural resourcesCurcuminFlow cytometryModelingThe Effectiveness of Natural Diarylheptanoids against Trypanosoma cruzi: Cytotoxicity, Ultrastructural Alterations and Molecular Modeling Studiesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/17889/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALSantiago VS The effectiveness of natural....pdfSantiago VS The effectiveness of 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| dc.title.pt_BR.fl_str_mv |
The Effectiveness of Natural Diarylheptanoids against Trypanosoma cruzi: Cytotoxicity, Ultrastructural Alterations and Molecular Modeling Studies |
| title |
The Effectiveness of Natural Diarylheptanoids against Trypanosoma cruzi: Cytotoxicity, Ultrastructural Alterations and Molecular Modeling Studies |
| spellingShingle |
The Effectiveness of Natural Diarylheptanoids against Trypanosoma cruzi: Cytotoxicity, Ultrastructural Alterations and Molecular Modeling Studies Santiago, Vitor Sueth Trypanosoma cruzi Recursos naturais Curcumina Citometria de fluxo Modelagem Trypanosoma cruzi Natural resources Curcumin Flow cytometry Modeling |
| title_short |
The Effectiveness of Natural Diarylheptanoids against Trypanosoma cruzi: Cytotoxicity, Ultrastructural Alterations and Molecular Modeling Studies |
| title_full |
The Effectiveness of Natural Diarylheptanoids against Trypanosoma cruzi: Cytotoxicity, Ultrastructural Alterations and Molecular Modeling Studies |
| title_fullStr |
The Effectiveness of Natural Diarylheptanoids against Trypanosoma cruzi: Cytotoxicity, Ultrastructural Alterations and Molecular Modeling Studies |
| title_full_unstemmed |
The Effectiveness of Natural Diarylheptanoids against Trypanosoma cruzi: Cytotoxicity, Ultrastructural Alterations and Molecular Modeling Studies |
| title_sort |
The Effectiveness of Natural Diarylheptanoids against Trypanosoma cruzi: Cytotoxicity, Ultrastructural Alterations and Molecular Modeling Studies |
| author |
Santiago, Vitor Sueth |
| author_facet |
Santiago, Vitor Sueth Moraes, Julliane de B B Sobral Alves, Eliomara Sousa Santos, Marcos André Vannier dos Lima, Célio Geraldo Freire de Castro, Rosane Nora Silva, Gustavo Peron Mendes Del Cistia, Catarina de Nigris Magalhães, Luma Godoy Andricopulo, Adriano Defini Sant'Anna, Carlos Mauricio Rabello de Ricardo, Debora Decoté Lima, Marco Edilson Freire de |
| author_role |
author |
| author2 |
Moraes, Julliane de B B Sobral Alves, Eliomara Sousa Santos, Marcos André Vannier dos Lima, Célio Geraldo Freire de Castro, Rosane Nora Silva, Gustavo Peron Mendes Del Cistia, Catarina de Nigris Magalhães, Luma Godoy Andricopulo, Adriano Defini Sant'Anna, Carlos Mauricio Rabello de Ricardo, Debora Decoté Lima, Marco Edilson Freire de |
| author2_role |
author author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Santiago, Vitor Sueth Moraes, Julliane de B B Sobral Alves, Eliomara Sousa Santos, Marcos André Vannier dos Lima, Célio Geraldo Freire de Castro, Rosane Nora Silva, Gustavo Peron Mendes Del Cistia, Catarina de Nigris Magalhães, Luma Godoy Andricopulo, Adriano Defini Sant'Anna, Carlos Mauricio Rabello de Ricardo, Debora Decoté Lima, Marco Edilson Freire de |
| dc.subject.other.pt_BR.fl_str_mv |
Trypanosoma cruzi Recursos naturais Curcumina Citometria de fluxo Modelagem |
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Trypanosoma cruzi Recursos naturais Curcumina Citometria de fluxo Modelagem Trypanosoma cruzi Natural resources Curcumin Flow cytometry Modeling |
| dc.subject.en.pt_BR.fl_str_mv |
Trypanosoma cruzi Natural resources Curcumin Flow cytometry Modeling |
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Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ); Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES); Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq); The State of São Paulo Research Foundation (FAPESP). |
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2016 |
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2016 |
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2017-02-23T13:49:11Z |
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2017-02-23T13:49:11Z |
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SANTIAGO, V. S. et al. The Effectiveness of Natural Diarylheptanoids against Trypanosoma cruzi: Cytotoxicity, Ultrastructural Alterations and Molecular Modeling Studies. Plos One, v. 11, n. 9, e0162926, 2016. |
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https://www.arca.fiocruz.br/handle/icict/17889 |
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1932-6203 |
| dc.identifier.doi.none.fl_str_mv |
10.1371/journal.pone.0162926 |
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SANTIAGO, V. S. et al. The Effectiveness of Natural Diarylheptanoids against Trypanosoma cruzi: Cytotoxicity, Ultrastructural Alterations and Molecular Modeling Studies. Plos One, v. 11, n. 9, e0162926, 2016. 1932-6203 10.1371/journal.pone.0162926 |
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Public Library of Science |
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Public Library of Science |
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